(Revised Abstract) DESCRIPTION (provided by applicant): This application outlines a research effort to develop and evaluate radiolabeled peptides for malignant melanoma imaging. Malignant melanoma is a serious public health problem due to an increase in its incidence and resistance to conventional chemotherapeutics and external beam radiation therapy. Early detection is critical for proper therapeutic management. There is a clear need to develop new and efficacious imaging and therapeutic agents. Our laboratory has developed a new class of metal-cyclized peptide (CCMSH) that target the a-MSH receptor present on melanoma cells. The CCMSH peptides will be radiolabeled with 99mTc, 111In for SPECT and 64Cu for PET imaging of melanoma in murine and human melanoma mouse models. Mice bearing solid tumors and metastatic melanoma in the lungs will be imaged at various times during the course of their disease to determine the detection sensitivity and specificity of the radiolabeled peptides. Micro SPECT and micro PET imaging studies will also be compared to determine the optimal combination of peptide, radionuclide and detection modality for melanoma imaging. The CCMSH imaging agents are envisioned to be part of a matched pair strategy for melanoma imaging and therapy in which the same melanoma targeting vector (CCMSH) can be radiolabeled with radioisotopes that possess imaging or therapeutic properties. We also plan to employ bacteriophage (phage) display technology to discover new melanoma targeting vectors. The random peptide libraries, displaying 5-150 peptides per particle, will be selected in human melanoma bearing mice for tumor targeting peptides. In vivo selection strategy should closely simulate the complex targeting environment an imaging agent encounters thus allowing us to select superior melanoma avid phage. We propose to use the tumor avid phage particles themselves as targeting agents in a pretarget approach. The tumor avid phage will be conjugated with <10 copies of Neutravidin per particle. Neutravidin phage will be injected into tumor bearing mice and allowed to localize to the tumor or clear the body over a period of day(s). Indium-111 labeled DTPA-biotin will be injected intravenously and the animals will be imaged over a period of several hours. Pretarget phage imaging will allow us to take advantage of the power of in vivo selection with polyvalent peptide display while not suffering the partitioning consequences of a large radiolabeled molecule.